Trifluoroacetic acid → Tamiphosphor Biotin

Participants

Reaction Steps

To a solution of 5-azido-1-pentanamine azide (46 mg, 0.36 mmol) and compound 19 (120 mg, 0.18 mmol) in t-BuOH/H2O (0.6 mL, v/v=1:1) was added tetrakis(acetonitrile)copper(I) phosphorus hexafluoride. The mixture was stirred at room temperature for 12 h, concentrated by reduced pressure, and purified on a by RP-18 reversed-phase column with elution of MeOH/H2O (1:9 to 9:1). The crude product of triazole compound was dissolved in 1,4-dioxane (1.0 mL), and added 1 M KOH(aq) (1.0 mL). The solution was stirred at 25° C. for 120 h (monitored by 1H NMR), and added Dowex 50W×8 to neutralize the solution. The mixture was filtered and concentrated under reduced pressure. The crude product (10 mg, 0.013 mmol) was dissolved in anhydrous DMF (0.1 mL), and biotin-OSu (4.5 mg, 0.013 mmol) and diisopropylethylamine (4.2 mg, 0.026 mmol) were added. The mixture was stirred at room temperature for 3 h, and concentrated under reduced pressure. The residue was dissolved in MeOH (0.5 mL), cooled to 0° C. in an ice bath, and added trifluoroacetic acid (0.16 mL, 2.1 mmol). The mixture was stirred for 1 h at room temperature, concentrated under reduced pressure, and purified on a RP-18 reversed-phase column with elution of MeOH/H2O (1:9 to 9:1) to give the title compound (40 mg, 30% overall yield). C33H57N10O7PS; yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.89 (1 H, s), 6.39 (1 H, d, J=19.6 Hz), 4.90 (1 H, t, J=5.2 Hz), 4.38 (1 H, t, J=7.2 Hz), 4.29-4.32 (1 H, m), 4.00 (2 H, m), 3.77-3.90 (2 H, m), 3.40-3.48 (2 H, m), 3.15-3.26 (2 H, m), 3.00 (1 H, t, J=5.2 Hz), 2.91-2.95 (2 H, m), 2.71 (1 H, d, J=12.8 Hz), 2.53-2.62 (2 H, m), 2.23 (2 H, t, J=7.2 Hz), 1.90-2.03 (5 H, m), 1.29-1.79 (16 H, m), 0.86-0.97 (6 H, m); 31P NMR (162 MHz, CDCl3) δ 13.6; HRMS negative mode calcd for C33H56N10O7PS: 768.3723, found: m/z 768.3723 [M−H]−.

Provenance & Evidence